Stakeholder-informed pragmatic trial protocol of the TabCAT-BHA for the detection of cognitive impairment in primary care.

Background: Cognitive impairment and dementia are frequently under-recognized. Health system strategies anchored in primary care are essential to address gaps in timely, comprehensive diagnosis. The goal of this paper is to describe the adaptation of a tablet-based brain health assessment (TabCAT-BHA) intervention and the study protocol to test its effectiveness in improving the detection of cognitive impairment, including dementia.

Safety of baclofen versus tizanidine for older adults with musculoskeletal pain.

Background: Baclofen and tizanidine are both muscle relaxants that carry the risk for neuropsychiatric events in older adults but there is a lack of data directly comparing their safety. This study aimed to investigate the relative risk between these two medications in causing injury and delirium in older adults.

Methods: This was a retrospective cohort study that was completed in an integrated healthcare system in the United States and included patients aged 65 years or older who started baclofen or tizanidine for the treatment of musculoskeletal pain from January 2016 through December 2018.

Dementia and readmission risk in patients with heart failure participating in a transitional care program.

Background: Cognitive impairment is prevalent in patients hospitalized for heart failure (HF). We aimed to generate further evidence on the value of dementia screening in hospitalized HF patients by examining whether and when dementia would be an independent risk factor for 30-day readmission while modeling permutations of known risk factors such as patient demographics, disease burden, prior utilization, and index hospitalization characteristics.

Methods And Results: A retrospective cohort study was employed, consisting of 26,128 patients (2,075 or 7.

Potentially Harmful Medication Dispenses After a Fall or Hip Fracture: A Mixed Methods Study of a Commonly Used Quality Measure.

Background: High-risk medication dispenses to patients with a prior fall or hip fracture represent a potentially dangerous disease-drug interaction among older adults. The research team quantified the prevalence, identified risk factors, and generated patient and provider insights into high-risk medication dispenses in a large, community-based integrated health system using a commonly used quality measure.

Methods: This was a mixed methods study with a convergent design combining a retrospective cohort study using electronic health record (EHR) data, individual interviews of primary care physicians, and a focus group of patient advisors.

Patient and Physician Perspectives of Deprescribing Potentially Inappropriate Medications in Older Adults with a History of Falls: a Qualitative Study.

Background: High-risk medications pose serious safety risks to older adults, including increasing the risk of falls. Deprescribing potentially inappropriate medications (PIMs) in older adults who have experienced a fall is a key element of fall reduction strategies. However, continued use of PIMs in older adults is common, and clinicians may face substantial deprescribing barriers.

Refining the Definition of Polypharmacy and Its Link to Disability in Older Adults: Conceptualizing Necessary Polypharmacy, Unnecessary Polypharmacy, and Polypharmacy of Unclear Benefit.

The term polypharmacy in older adults is generally used in a pejorative context in the medical literature. Because of its link to geriatric syndromes and disability, the avoidance of polypharmacy is usually recommended in older adults as a strategy to optimize functional status. However, there are many polypharmacy regimens based on high-quality trials that clearly reduce the risk of disability in older adults.

Age-Dependent Hemoglobin A1c Therapeutic Targets Reduce Diabetic Medication Changes in the Elderly.

Objective: To assess whether implementation of age-dependent therapeutic targets for high hemoglobin A1c (HbA1c) changed clinicians' ordering of diabetes medications for older adults.

Background: In 2016, Kaiser Permanente Southern California (KPSC) changed the therapeutic targets for alerting clinicians about high HbA1c results in the electronic health record, KP HealthConnect (KPHC). Previously, all HbA1c results ≥7.

The Risk of Pneumonia in Older Adults Using Nonbenzodiazepine Hypnotics.

Background: Previous studies have shown an increased risk of pneumonia with benzodiazepines (BZD) and an increased risk of any infection with non-BZD hypnotics, but no analysis has specifically investigated the risk of pneumonia with non-BZD hypnotic use.

Objective: To evaluate the risk of pneumonia associated with non-BZD hypnotic use in the elderly.

Methods: This was a retrospective case-control study of members aged 65 years and older enrolled in an integrated health care system.

Improving Care in Older Patients with Diabetes: A Focus on Glycemic Control.

Diabetes affects more than 25% of Americans older than age 65 years. The medical care of older patients must differ from the care of their younger counterparts. Older patients are at high risk of drug toxicity.

Risk of Injury in Older Adults Using Gastrointestinal Antispasmodic and Anticholinergic Medications.

Objectives: To determine the risk of injury associated with gastrointestinal (GI) antispasmodic and anticholinergic use in elderly adults.

Design: Retrospective case-control study.

Setting: Integrated healthcare system.

Targeting Mitochondria with Avocatin B Induces Selective Leukemia Cell Death.

Treatment regimens for acute myeloid leukemia (AML) continue to offer weak clinical outcomes. Through a high-throughput cell-based screen, we identified avocatin B, a lipid derived from avocado fruit, as a novel compound with cytotoxic activity in AML. Avocatin B reduced human primary AML cell viability without effect on normal peripheral blood stem cells.

Mitochondrial DNA damage by bleomycin induces AML cell death.

Mitochondria contain multiple copies of their own 16.6 kb circular genome. To explore the impact of mitochondrial DNA (mtDNA) damage on mitochondrial (mt) function and viability of AML cells, we screened a panel of DNA damaging chemotherapeutic agents to identify drugs that could damage mtDNA.

DNA ministrings: highly safe and effective gene delivery vectors.

Conventional plasmid DNA vectors play a significant role in gene therapy, but they also have considerable limitations: they can elicit adverse immune responses because of bacterial sequences they contain for maintenance and amplification in prokaryotes, their bioavailability is compromised because of their large molecular size, and they may be genotoxic. We constructed an in vivo platform to produce ministring DNA-mini linear covalently closed DNA vectors-that are devoid of unwanted bacterial sequences and encode only the gene(s) of interest and necessary eukaryotic expression elements. Transfection of rapidly and slowly dividing human cells with ministring DNA coding for enhanced green fluorescent protein resulted in significantly improved transfection, bioavailability, and cytoplasmic kinetics compared with parental plasmid precursors and isogenic circular covalently closed DNA counterparts.

Glucopsychosine increases cytosolic calcium to induce calpain-mediated apoptosis of acute myeloid leukemia cells.

To identify novel anti-cancer agents, we created and screened a unique nutraceutical library for activity against acute myeloid leukemia (AML) cells. From this screen, we determined that glucopsychosine was selectively toxic toward AML cell lines and primary AML patient samples with no effect toward normal hematopoietic cells. It delayed tumor growth and reduced tumor weights in mouse xenograft models without imparting toxicity.

Making hospitals safer for older adults: updating quality metrics by understanding hospital-acquired delirium and its link to falls.

The medical care of hospitalized geriatric patients must differ from the care of younger adults. Because of reduced "reserve capacity," hospitalized older adults are at high risk of development of geriatric syndromes such as delirium and falls. Geriatric syndromes often lead to functional decline and dependence.

Risk of injury associated with skeletal muscle relaxant use in older adults.

Background: The use of skeletal muscle relaxants (SMRs) among older adults is associated with sedation and confusion, which may lead to an increased risk of falls and injuries. SMRs continue to be used among older adults, although they are on the Beers list as drugs to avoid in the elderly.

Objective: To investigate the relationship between SMR use and subsequent risk of injury.

Making the hospital safer for older adult patients: a focus on the indwelling urinary catheter.

The needs of hospitalized geriatric patients differ from the needs of hospitalized younger adults. In an attempt to improve systems of care for the older adult, the Centers for Medicare and Medicaid Services classified urinary tract infections related to the use of indwelling urinary catheters (IUC) as one of eight "never events." The insertion of an IUC is a commonly performed procedure that can cause an array of iatrogenic complications.

The impact of HER-2 status on local recurrence in women with stage I-II breast cancer treated with breast-conserving therapy.

This study was undertaken to determine whether overexpression of the oncogene HER-2 is associated with an increase in local recurrence in women with early stage breast cancer treated with breast-conserving therapy (BCT). A retrospective review of the medical records of all women treated with stage I-II invasive breast cancer from 1991 through 2001 was performed. Of 596 eligible patients treated in that time period, immunohistochemical testing for HER-2 expression was performed in 352 patients (59%): 266 patients (76%) were HER-2 negative and 86 patients (24%) were HER-2 positive.

Inactivation of the mitotic checkpoint as a determinant of the efficacy of microtubule-targeted drugs in killing human cancer cells.

Drugs that disrupt microtubule dynamics include some of the most important of cancer chemotherapies. While these drugs, which include paclitaxel (Taxol), are known to invoke the mitotic checkpoint, the factors that determine cancer cell killing remain incompletely characterized. Cells that are relatively resistant to killing by these drugs block robustly in mitosis, whereas cells sensitive to killing block only transiently in mitosis before undergoing nuclear fragmentation and death.